3-Methoxy-4-hydroxy-D-mandelic acid, a urinary metabolite of norepinephrine

Studies on the Biogenesis and Metabolism of Norepinephrine in Patients With Pheochromocytoma*

“…In vivo. While the measurement of 3-methoxy-4-hydroxymandelic acid is a useful means of diagnosing pheochromocytoma (19), another possible approach is revealed by the findings of LaBrosse, Axelrod and Sjoerdsma (24) in two of our patients. Making quantitative use of paper chromatography, it was found that Patients 1 and 7 were excreting about 20 mg. of 3-methoxy-4-hydroxymandelic acid per day but also 10 to 30 mg. of normetanephrine when the norepinephrine excretion was approximately 2 mg. per day.…”

“…The norepinephrine from the first day's collection was isolated and recrystallized and its radioactivity measured. The results obtained are shown in (19) reported the isolation of 3-methoxy-4-hydroxymandelic acid from human urine and showed that it was a major product of norepinephrine metabolism. Axelrod (20) then showed that the 3-hydroxy position of norepinephrine can be methylated by animal tissues; he also presented evidence (21) that o-methylation followed by oxidative deamination is the major pathway of metabolism in rats.…”

Simplified assay method for measuring 3-methoxy-4-hydroxy mandelic acid in human urine.

“…3-methoxy-4-hydroxy mandelic acid or vanillyl mandelic acid (VMA) was first detected by Armstrong et al (1957)1) in normal human urine as one of the metabolites of catecholamines (CA) 2-5) VMA and its parent substances, noradrenaline and adrenaline are known to be excreted in abnormal amounts in patients with pheochromocytomas4,6). We could easily give here several examples of reports dealing with urinary CA excretion in various stressful situations7-13).…”

Metabolism of Noradrenaline in the Human*

“…They not only showed something about the cleavage of adrenaline but pointed out that there were at least five or six urinary catabolites of adrenaline. In 1957 Armstrong, McMillan and Shaw (18,19) identified 3-methoxy-4-hydroxymandelic acid as a major urinary metabolite of adrenaline in the human.Subsequently, Axelrod and associates (20,21) isolated metadrenaline (3-0-methyladrenaline) and normetadrenaline (3 -0-methylnoradrenaline) from rat urine and metadrenaline from human urine. Also in 1957 von Euler (22) demonstrated 3,4-dihydroxymandelic acid in human urine, and in 1958 LaBrosse, Axelrod and Sjoerdsma (23) isolated normetadrenaline from the urine of pheochromocytoma patients.…”

“…They not only showed something about the cleavage of adrenaline but pointed out that there were at least five or six urinary catabolites of adrenaline. In 1957 Armstrong, McMillan and Shaw (18,19) identified 3-methoxy-4-hydroxymandelic acid as a major urinary metabolite of adrenaline in the human.…”